Background Ovarian cancer is a lethal disease comprised of distinct histopathological types. There are few established biomarkers of ovarian cancer prognosis, in part because subtype-specific associations may have been obscured in studies combining all subtypes. We examined whether progesterone receptor (PR) and estrogen receptor (ER) protein expression were associated with subtype-specific survival in the international Ovarian Tumor Tissue Analysis (OTTA) consortium. Methods PR and ER were assessed by central immunohistochemical analysis of tissue microarrays for 2933 women with invasive epithelial ovarian cancer from 12 study sites. Negative, weak, and strong expression were defined as positive staining in <1%, 1–50%, and ≥50% of tumor cell nuclei, respectively. Hazard ratios (HRs) for ovarian cancer death were estimated using Cox regression stratified by site and adjusted for age, stage, and grade. Results PR expression was associated with improved survival for endometrioid (EC; p<0·0001) and high-grade serous carcinoma (HGSC; p=0·0006), and ER expression was associated with improved EC survival (p<0·0001); no significant associations were found for mucinous, clear cell, or low-grade serous carcinoma. EC patients with hormone receptor (PR and/or ER) positive (weak or strong) versus negative tumors had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·33; 95% CI, 0·21–0·51; p<0·0001). HGSC patients with strong versus weak or negative tumor PR expression had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·71; 95% CI, 0·55–0·91; p=0·0061). Interpretation PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to determine whether hormone receptor status predicts response to endocrine therapy, and can guide personalized treatment for ovarian cancer. Funding Carraressi Foundation, US National Institutes of Health, National Health and Medical Research Council of Australia, UK National Institute for Health Research, and others.

Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (Ptrend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (Ptrend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (Ptrend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk.

This is a pre-copyedited, author-produced version of an article accepted for publication in Nature Genetics following peer review. The version of record "Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries"

The adductor muscle of the pen shell Atrina pectinata (AMPS) is a popular protein‐enriched food item in Asian Pacific countries, and has only been marketed in the frozen condition, as a result browning and decreased sensory attributes occur. To overcome these problems, superheated steam roasting (at 270°C for 4 min) combined with the hot smoke (10 min) using a selective Oak sawdust was employed to develop a new AMPS product yielding high physicochemical properties during storage periods (0–13 days) especially at 10°C. The processed AMPS showed high sensory preferences because of good odor, color, and textural properties. It also significantly inhibited bacterial growth, volatile basic nitrogen, thiobarbituric acid‐reactive species, and pH changes, and eventually possessed higher nutritional composition with low trimethylamine N‐oxide level. Results indicate that saturated steam allows AMPS at good physicochemical conditions, whereas hot smoke‐derived aroma compounds prolong its shelf life through antioxidant and antimicrobial activities.

Background Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. Design and methods BL tissues from residual tissue repositories, and 2 academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV early RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student’s t-test. Results Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age-group 0-19 to 55% in age-group 20-34, and fell to 25% in age-group 60+ years, P=0.08); with race (56% in Blacks/Hispanics versus 21% in Whites/Asians/Pacific Islanders, P=0.006); and by HIV status (64% in HIV positive versus 22% in HIV negative cases, P=0.03). Conclusions EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.

Ghrelin is a 28-amino acid brain-gut peptide isolated from rat and human stomach, which is the first endogenous ligand of growth hormone secretagogue receptor 1a (GHSR-1a). 1)Ghrelin exists in the body in two forms: n-octanoyl-ghrelin (ghrelin), which contains an n-octanoyl modification at serine-3 and forms ghrelin's mark structure, and unacylated ghrelin (des-ghrelin). Acylated ghrelin is required for GHSR1a, whereas the unacylated form does not bind to GHSR1a. 2,3) GHSR-1a is widely expressed in peripheral and central tissues, including the hypothalamus, hippocampus and cortex. 4,5) Although ghrelin is predominantly produced in the X/A-like cells of the stomach in rodents, it is expressed in many other peripheral tissues and in the central nervous system 6) ; therefore, ghrelin has extensive biological action, such as stimulating food intake, regulating the secretion of gastric acid, gastric motility, 7) simulating insulin secretion, 8) modulating cell proliferation and survival, 5,9,10) immunological regulation and an anti-inflammatory effect, 11) as well as improving learning and memory, 12) the impairment of which is an Alzheimer's Disease (AD) phaenotype.AD, a devastating neurodegenerative condition, has become the fourth most fatal disease, following heart disease, cancer and stroke. AD has two pathological hallmarks: bamyloid (Ab) deposition and neurofibrillary tangles, which contain hyperphosphorylated tau protein and have a positive relation with cognitive dysfunction. In the process of tau phosphorylation, glycogen synthase kinase-3b (GSK-3b) plays an important role. Schubert demonstrated that disturbance of the insulin signaling system results in phosphorylation, whereas phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway dysfunction, which causes GSK-3b activity increase and leads to tau hyperphosphorylation. 13) Recently, some studies have indicated that AD is related to a brain insulin-resistant state that results in glucose utilization abnormalities.14) However, insulin resistance is a critical mechanism associated with type 2 diabetes and AD. Diabetic patients with insulin resistant type 2 diabetes have a 30-65% increased risk for developing AD. Type 2 diabetes is an independent risk factor for the disease. De la Monte and Wands indicated that Alzheimer's Disease could be a "type 3 diabetes." 15) Hyperglycemia, a fundamental biochemistry characteristic in diabetics, has an important role in diabetes. Hyperglycemia in type 2 diabetes is not only a secondary manifestation of insulin resistance, but could also be responsible for directly inducing insulin resistance in the target tissue. 16)However, whether a neuron is an insulin-sensitive cell is still a matter of controversy. [17][18][19] Studies have shown that hyperglycemia is a primary cause of nervous system impairment. 20) Evidence indicates that ghrelin may modulate insulin sensitivity, stimulate insulin-induced glucose uptake, 21) and modulate memory.12) Therefore, we hypothesized that ghrelin may promote hippocampal neuronal glu...

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